In incipient heart failure, ventricular hypertrophy is generally considered a compensatory response to ventricular overload; however, the precise biophysical dynamics of this response have not been worked out. The objective of this project is to define the biophysical interrelations between contractility, load and wall stress in the intact hypertrophied and failed ventricle. These studies are designed to answer the following questions: 1) Is the ventricle subjected to subtle progressive increases in wall load? 2) Is stress on the cardiac muscle fiber held constant by increases in wall thickness as force in the ventricular wall increases? 3) Does failure occur when stress on the fiber exceeds the ability of the fiber to contract against it? 4) Does the failing heart become refractory to digitalis and sympathetic stimulation? Precision strain gauge methodology will be employed to study the interrelations of contractility, load and wall stress in intact dogs subjected to chronic ventricular pressure and volume overload. In four groups of animals (normal, immediate post overload, compensated and heart failure) the function of the ventricle within the Frank-Starling Framework as well as ventricular response to altered pressor-inotropic states induced by norepinephrine, isoproterenol and ouabain will be measured. These experiments are intended to define the progressive alterations in ventricular dynamics during compensation and overt failure.